BMEGSA Exchange: Maung Zaw Win
“The Effect of Cellular Architecture on Functional and Mechanical Properties”
Recently, there has been a push towards clinical translation of biomechanical models of tissues by developing patient-specific models to predict disease outcomes. To accomplish this, it is necessary to understand the functional and mechanical properties of all the tissue components, including individual cells. In vasculature, tissues and cells have different structures based on their functional role. The principle goal of this work is to determine how cellular architecture influences function and mechanical properties. To test our hypotheses, we have developed in vitro models to study the relationship between structure and function at the tissue and cellular scale. We have developed microfluidic capture array device (MCAD) technology (Fig. 1) to study cell structure and function in 2D engineered vascular smooth muscle tissue and have developed cellular micro-biaxial stretching (CμBS) microscopy (Fig. 2) to determine single cell mechanical properties. Using MCAD technology we are able to vary initial cell-cell contact during seeding to bias the cellular architecture in confluent vascular smooth muscle tissues. We found that tissues seeded using initially higher cell–cell contact conditions yielded tissues with a more elongated cellular architecture which lead to greater contractile function in engineered tissues. We have also developed CμBS microscopy to determine the anisotropic mechanical properties of individual cells, which we employ to determine the full mechanical description (given by the strain energy density function) of vascular smooth muscle cells. Using our method, we find that smooth muscle cells with native-like architectures are highly anisotropic and can be described by a general strain energy density function based on the actin cytoskeletal organization. Our results suggest that structural organization of cells in organs affect their functional and mechanical properties.
BME Seminar Series: Dr. Rouzbeh Amini, University of Akron
“Multi-scale Framework for Analysis of Tricuspid Valve Biomechanics “
Mechanics plays a critical role in tissue development, regeneration, and remodeling, as cell-cell interactions and cellmatrix interactions are known to be heavily influenced by changes in the mechanical microenvironment at the extracellular matrix (ECM)/cellular level. In the tricuspid valve (TV), located between the right ventricle and the right atrium in the heart, the leaflets open and close more than three billion times during their lifetime. Thus, TV cells and ECM maintain their homeostasis while subjected to a highly dynamic loading environment. Considering the hierarchy of the living system (i.e. heart, valves, leaflets, and ECM/cellular levels in the case of TV), it is imperative to study biomechanics and mechanobiology using multi-scale approaches. Unfortunately, such multi-scale frameworks do not currently exist, and a main goal of our research lab is to combine experimental techniques and computational simulation to address such major limitations. We are particularly interested in understanding why TV surgery has poor long-term success rate (30% to 40% of patients who undergo surgery have had a recurrence of valve problems). We aim to understand how tricuspid valve repair procedures will affect the valve’s function at the tissue level and at the ECM (micro) level, as we believe that surgical alterations cause changes in tissue stress and tissue microstructure in ways that can eventually lead to failure of the repaired valve.
Dr. Amini completed a Ph.D. in Biomedical Engineering at the University of Minnesota in the field of ocular biomechanics and biotransport in 2010. He then continued his research work on the mechanics of soft tissue as a postdoctoral trainee at the University of Pittsburgh’s Department of Bioengineering, where he held the Ruth L. Kirschstein National Research Service Award (NIH F32). He conducted his postdoctoral research on the biomechanics of cardiac valves. Dr. Amini has served as an assistant professor in the Department of Biomedical Engineering at The University of Akron since August 2013. The overall goal of his research laboratory is to improve human health by studying the multi-scale biomechanics and biotransport in cardiovascular, ocular, and digestive systems. Dr. Amini’s research has been funded by the Akron Children’s Hospital, Firestone Foundation, and American Heart Association.
BME Seminar Series: Dr. Lori Setton, Washington University in St. Louis
Dr. Setton is the elected president of the Biomedical Engineering Society (BMES).
“The Stressful Life of the Intervertebral Disc Cell”
Intervertebral disc disorders contribute to pain and disability in millions of affected individuals annually, contributing to low back pain’s ranking as #1 in disease impact in the USA. Pathological processes for resident cells of the intervertebral disc, the nucleus pulposus cells, contribute to premature cell death that can drive loss of intervertebral disc height, tissue destruction and herniation. These nucleus pulposus cells are derived from notochord, unlike the neighboring mesenchymal cells, and are responsible for tissue synthesis and growth in the neonate. With loss of this cell population in the first decades, the intervertebral disc experiences altered disc biochemical composition, cellularity, and material properties that are major contributors to disc pathology. Our laboratory has studied factors that regulate nucleus pulposus cell phenotype and demonstrated an ability to promote biosynthesis and survival through interactions with laminin matrix proteins. We have also advanced knowledge of environmental cues that promote a healthy, biosynthetically active nucleus pulposus cell, factors that can be manipulated to attenuate inflammatory cytokine expression, promote matrix biosynthesis, and control progenitor cell differentiation. In this talk, we will describe our work with engineering substrates and protein-conjugated biomaterials to deliver cells to the disc for regeneration purposes.
Dr. Setton received her B.S.E. from Princeton University in Mechanical and Aerospace Engineering, with M.S. and Ph.D. degrees in Mechanical Engineering from Columbia University. Dr. Setton joined the Department of Biomedical Engineering at Duke University in 1994, where she served as the Bevan Distinguished Professor of Biomedical Engineering and Orthopaedic Surgery. Dr. Setton recently joined the Department of Biomedical Engineering at Washington University to accept the position as Lopata Distinguished Pofessor of Biomedical Engineering & Orthopaedic Surgery.
Dr. Setton’s research focuses on understanding the mechanisms for degeneration and regeneration of soft tissues of the musculoskeletal system. Recent work focuses on development of in situ forming hydrogels for drug delivery and tissue regeneration in the knee joints and spine. She has funded her lab through grants from the NIH, NSF, Whitaker Foundation, Coulter Foundation, OREF, AO Foundation, and research agreements with many corporations.
Dr. Setton has over 180 publications and has licensed several patents for commercial development. She has served on the Editorial Advisory Boards of the Annual Reviews of Biomedical Engineering, Journal of Biomechanical Engineering, Osteoarthritis and Cartilage, and Journal of Biomechanics. Dr. Setton has also served as a permanent member of NIH and NSF study sections, as a consultant to NIH and AAOS, and on the Boards of the Biomedical Engineering Society, Orthopaedic Research Society and World Council on Biomechanics. She is currently serving as President of the Biomedical Engineering Society from 2016-2018. Dr. Setton is a Fellow of the BMES, the AIMBE and has received a PECASE Award, Dean’s Award for Outstanding Research, Graduate Dean’s Award for Excellence in Mentoring, and ASME’s Mow Medal.
Speaker: Dr. Patric Glynn, Stitch Fix; Data Scientist, Client Algorithms
Title: “Data Science: A Nontraditional Career Option that Combines Experimentation, Programming, Math, and Statistics“
Choosing whether to pursue a career in academia or industry is a big decision. For individuals who choose industry, there are many diverse job options, including research scientist, product engineer, and others. In recent years, an additional career choice has surfaced for those that possess skills in experimentation, programming, math, and statistics: Data Science.
In this talk, I will discuss how Data Science can be a viable, fulfilling career path for Biomedical Engineering students looking for a nontraditional industry role. Specifically, we will cover:
- What is Data Science?
- What do Data Scientists do?
- How do the skills and training in Biomedical Engineering apply to Data Science?
I will also cover how being successful at a high-growth silicon valley technology company requires a different project and experimentation approach when compared to traditional academic research.
Dr. Patric Glynn received his B.S. in Biomedical Engineering from Case Western Reserve University in 2009 and his Ph.D. in Biomedical Engineering from The Ohio State University in 2015. While working on his Ph.D., he received an American Heart Association Predoctoral Fellowship. Dr. Glynn worked as a Data Scientist at Nationwide Insurance before moving out to San Francisco, where he has spent the last 1.5 years as a Data Scientist at Stitch Fix. At Stitch Fix, he is a member of the Client Algorithms team, where he focuses on researching and implementing company strategies for algorithmic approaches to customer retention and reengagement.
Speaker: Dr. Matthew Becker, Associate Dean for Research; W. Gerald Austen Endowed Chair in Polymer Science and Polymer Engineering
Affiliation: University of Akron
Title: Building bone with polymers – How new materials and additive manufacturing are changing medicine
Recent synthetic advances have enabled the synthesis of polymers designed to elicit specific cellular functions and to direct cell-cell interactions. Motivated by traumatic injuries experienced by warfighters, we are developing novel materials and devices designed to repair segmental bone defect and achieve limb salvage. Biomimetic approaches based on polymers derivatized with adhesive receptor-binding peptides glycoproteins and tethered growth factors have been reported to enhance interactions at the biotic-synthetic interface. Further advances in both synthetic methodology and scaffold fabrication are needed to drive these efforts forward. This presentation will describe the use of several translationally relevant chemistries and functionalization strategies that are impacting the practice of medicine and how physicians are planning for future therapies that were not possible previously.
Matthew L. Becker is the W. Gerald Austen Endowed Chair of Polymer Science and Polymer Engineering and The Associate Dean for Research in the College of Polymer Science and Polymer Engineering at The University of Akron. His multidisciplinary research team is focused on developing bioactive polymers for regenerative medicine and addressing unmet medical needs at the interface of chemistry, material science and medicine. He is the founder of three start-up companies. He earned a PhD in organic chemistry at Washington University in St. Louis as an NIH Chemistry Biology Interface Training Fellow. In 2003, Dr Becker moved to the Polymers Division of the National Institute of Standards and Technology for a NRC Postdoctoral Fellowship. He joined the permanent staff as a project leader in 2005 before moving to The University of Akron in 2009. Professor Becker was awarded the ACS Publications Macromolecules-Biomacromolecules Young Investigator Award in 2015 and is a fellow of the ACS PMSE Division and the Royal Society of Chemistry.
Speaker: Dr. Yizhou Dong
Affiliation: The Ohio State University
Title: Development of nanomaterials for mRNA therapeutics and genome editing
Messenger RNA (mRNA) therapeutics have shown great promise for purpose of expressing functional proteins. However, the efficient and safe delivery of mRNA remains a key challenge for the clinical application of mRNA based therapeutics. Lipid and lipid-like nanoparticles possess the potential for mRNA delivery. Based on our previous experiences, we have designed and synthesized N1,N3,N5-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide (TT). We applied an orthogonal experimental design to investigate the impacts of formulation components on delivery efficiency. TT3 LLNs, a lead material fully recovered the level of human factor IX (hFIX) to normal physiological values in FIX-knockout mice. In addition, we demonstrated that TT3 LLNs were capable of effectively delivering Cas9 mRNA and guide RNA to the mouse liver for genome editing.
Dr. Dong received his Ph.D. degree in pharmaceutical sciences from the University of North Carolina at Chapel Hill (UNC-CH) in 2009 under the supervision of Professor K.-H. Lee. He was a postdoctoral fellow from 2010-2014 in Children’s Hospital Boston at Harvard Medical School and also in the David H. Koch Institute for Integrative Cancer Research at MIT in the laboratory of Professors Robert Langer and Daniel Anderson. He also holds B.S. in pharmaceutical sciences from Peking University, Health Science Center (2002) and M.S. in organic chemistry from Shanghai Institute of Organic Chemistry (2005). He joined the Division of Pharmaceutics and Pharmaceutical Chemistry at The Ohio State University as Assistant Professor in 2014.
Speaker: Dr. Forrest Kievit, Assistant Professor of Biomedical Engineering
Affiliation: University of Nebraska-Lincoln
Speaker: Dr. Eben Alsberg; Professor, Biomedical Engineering and Orthopaedic Surgery & Director, Stem Cell and Engineering Novel Therapeutics Laboratory
Title: Modular Inductive High-Density Cell Culture Systems for Engineering Complex Tissues
Affiliation: Case Western Reserve
“Modular Inductive High-Density Cell Culture Systems for Engineering Complex Tissues”
High-density cultures of cells can mimic immature condensates present during many developmental and healing processes. Presenting specific soluble signals, such as growth factors, exogenously in tissue culture media can regulate cell behavior in these cultures and promote new tissue formation. However, shortcomings of this approach include transport issues, limited spatial control over signal presentation, and required repeated dosing in the media. We have engineered technology that overcomes these challenges by incorporating polymer microspheres containing bioactive signals within the high-density cell cultures, which permits localized spatial and temporal control over the presentation of these regulatory cues to the cells. In this talk, I will present our research using this strategy to engineer a variety of tissues, including bone, cartilage and trachea. The capacity to deliver diverse signals, including growth factors and plasmid DNA, for driving new tissue formation will be demonstrated. In addition, the value of this technology for engineering a wide range of tissue shapes, including spheres, sheets, rings and tubes will be shown. Finally, the utility of providing cell-instructive bioactive factors from biomaterials in a controlled manner for the assembly of modular tissue units to engineer complex constructs comprised of multiple tissue types will be explored.
Dr. Alsberg took a faculty position in 2005 at Case Western Reserve University, where he is currently Professor of Biomedical Engineering and Orthopaedic Surgery and serves as Director of the Stem Cell and Engineered Novel Therapeutics Laboratory. His lab focuses on the engineering of new technologies to regenerate tissues and treat diseases through the development of novel biomaterials and microenvironments. He’s co-authored over 100 peer reviewed papers and book chapters, and his work has been recognized with the 2008 Ellison Medical Foundation New Scholar in Aging Award, the Crain’s Cleveland Business 2009 Forty Under 40 Award, a Visiting Professorship at Kyung Hee University (Korea) and a Lady Davis Fellowship at the Technion (Israel). The NIH, DOD, NSF, the Ellison Medical Foundation, the Coulter Foundation, the Musculoskeletal Transplant Foundation, the State of Ohio and the AO Foundation have funded his lab’s research.
Speaker: Dr. Frederic Heim, Professor, R&D Manager at GEPROVAS
Affiliation: Université de Haute Alsace
Title: Heart Valves from Fibers: Remaining Challenges
Over 300.000 heart valves are replaced every year in western countries and valve therapy represents today one of the most common surgical procedures performed in the world. While open chest surgery remains the gold standard to replace a faulty valve, less invasive approaches have been developed over the last decade. Actually, the rapid developments and success in percutaneous vascular stents implantation over the last 2 decades to treat vessel stenosis has made this technique attractive today even for aortic valve replacement. The principle is to implant a stented valve prosthesis by going through the vascular network of the patients. With this new technique, patients are not exposed to the risks of surgery, and transcatheter aortic valve implantation (TAVI) has become highly suitable for an increasing elderly population and has become an accepted alternative technique to surgical valve replacement for over 150,000 patients worldwide. Despite minor issues related to the implantation of the device, this non-invasive technique is cost-effective and provides increased comfort to patients, relative to traditional surgical valve implantation. In a fast growing global market, where TAVI related survival rates depend highly on the initial patient’s health, one can expect that more less-critical patients could be treated successfully with TAVI in the coming years. Currently, the valve material used in TAVI is biologic tissue, such as bovine or porcine pericardium. However, once assembled inside the metallic stent and crimped at low diameter for catheter insertion, studies have shown that the biological materials may become degraded. Textile polyester (PET) could be considered as an alternative material to replace TAVI biological valve leaflets. In particular, woven textile constructions have outstanding folding and resistance properties and as a result, these materials are easy to crimp and insert, even in low profile devices. Moreover, woven materials are discontinuous, mitigating the risk of a catastrophic rupture. Rupture propagation is isolated to the single filament. Recent works showed that woven textile materials could resist up to over 200 million cycles in vitro under accelerated cyclic loading and 6 months in vivo successful implantations were reported with fabric valve prototypes implanted in juvenile sheep models. However, despite the high potential of the material, challenges remain before textile can be considered as a durable valve replacement solution.